The nucleosome structure of chromatin has been conserved between widely divergent species over millions of years of evolution and must therefore be particularly suited to performing the processes of trascription and replication. The process of cell differentiation, the stablity of the differentiated state and the clonality of X-chromosome inactivation and inheritance demand that there exist mechanisms both to alter and maintain the expression of selected genes across cell generations. Using a density gradient sedimentation equilibrium analysis, we will attempt to describe a mechanism whereby transcriptional information may be vertically transmitted by the nucleosomal proteins. With protein crosslinking, controlled proteolysis and electron microscopy we will define the specific protein-protein interactions involved in nonhistone-nucleosome binding, nucleosome communication and chromatin superstructure. Experiments using cytosine arabinoside will allow us to functionally isolate the synthesis of DNA and study the allied replicative processes of histone and nonhistone synthesis, chromosomal protein deposition, nucleosome assembly and chromatin maturation. These processes will be assayed in cultured cells and in in vitro replication systems using nuclease digestion, gel electrophoresis, protein crosslinking and nucleic acid hybridization.